One goal of antiretroviral therapy (ART) in immunocompromised HIV-infected individuals is immune reconstitution. Since its introduction, ART has led to declines in AIDS-associated morbidity and mortality. These benefits, in part, arise from increases in CD4+ cell counts and decreases in plasma HIV viral titers. However, following initiation and withdrawal of ART, opportunistic infections (OIs) and other HIV-related events can, and often do, still occur. These events can, in certain instances, create a cytokine storm of varying severity. Thus, the resulting increase in immune function can cause an exaggerated response to a disease or other pathogen leading to immune reconstitution inflammatory syndrome (IRIS). IRIS can occur at any CD4+ count and at any time during the administration of ART, though it usually presents within the first 4 to 8 weeks after (re)initiation of ARV therapy.
There is currently no standard of care for treating IRIS. Thus, the onset of IRIS in an immunodeficient individual (such as HIV patients) can rapidly become severe resulting in increased morbidity and mortality of HIV patients. What is more, there is no determinant factor whether an individual will develop IRIS, and if they do how severe the IRIS will be. Thus, there is a need in the art for therapies to prevent, treat, and modulate IRIS in immunodeficient patients, particularly in HIV patients undergoing ART. Solutions to this and other problems in the art are provided herein.